Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/Phenylbutyrate
Phenylbutyrate is an approved drug used for treating urea-cycle disorders. It has recently been found to boost the expression of the DJ1 gene, reduce alpha-synuclein aggregation and more recently to attenuate the production of pro-inflammatory agents and reactive oxygen species by the microglia. This raises hopes that it may have therapeutic application in the control of the inflammation and oxidative stress that appear to be part of the pathogenetic processes in neurodegenerative diseases such as Parkinson's.
Gardian et al  found that the application of phenylbutyrate to MPTP induced neurons reduced damage to the substantia nigra.
Zhou et al  found that In a transgenic mouse model of diffuse Lewy body disease, long-term administration of phenylbutyrate reduces α-synuclein aggregation in brain and prevents age-related deterioration in motor and cognitive function.
We conclude that drugs that up-regulate DJ-1 gene expression may slow the progression of Parkinson disease by moderating oxidative stress and protein aggregation.
Freed and Zhou  have applied for funding to conduct an extended trial of phenylbutyrate.
Roy et al  have demonstrated that Sodium Phenylbutyrate (NaPB)
"inhibits nigral expression of proinflammatory molecules and the activation of glial cells, increases the level antioxidant GSH in the [Substantia Nigra pars compacta] , protects the loss of dopaminergic neurons, and improves the behavioral functions in MPTP-intoxicated mice. These results highlight undiscovered properties of NaPB and indicate that NaPB may be used for therapeutic intervention in PD or neurodegenerative disorders."
Michael J. Fox Foundation, Searchable database of PD-related research grants.
Phenylbutyrate to Prevent Progression of Parkinson's Disease.
Use the following links to query the PubMed, PubMed Central and Google Scholar databases using the Search terms:- Parkinson's_Disease Phenylbutyrate.
This will list the latest papers on this topic. You are invited to update this page to reflect such recent results, pointing out their significance.
- Substances with possible neuroprotective properties:
- Caffeine,--Celastrol,--Co-Enzyme Q10,--Creatine,--DHA,--Exendin-4 (EX-4),--GDNF,--Glutathione (GSH),--GM1,--Isradipine,--Melatonin,--Minocycline,--Nicotine,--NSAIDs,--Phenylbutyrate,--Phytic Acid,--Probucol,--Quinoxaline,--Rasagiline,--Riboflavin,--Statins,--Tolcapone,--Urate & Uric Acid,--Vitamin D,--Vitamin E,--
- Gardian, G.; Yang, L; Cleren, C.; Calingasan, N. Y.; Klivenyi, P. and Beal, M. F. (2004) Abstract Neuromolecular Med. 5 (3):235 - 241. Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity. http://www.ncbi.nlm.nih.gov/pubmed/15626823
- Zhou W.; Bercury, K.; Cummiskey, J.; Luong, N.; Lebin, J. and Freed, C. R. (2011) Abstract J. Biol. Chem. 286(17):14941 – 14951 Phenylbutyrate up-regulates the DJ-1 protein and protects neurons in cell culture and in animal models of Parkinson disease. http://www.ncbi.nlm.nih.gov/pubmed/21372141
- Roy, Avik, Anamitra Ghosh, Arundhati Jana, Xiaojuan Liu, Saurav Brahmachari, Howard E. Gendelman, and Kalipada Pahan. “Sodium Phenylbutyrate Controls Neuroinflammatory and Antioxidant Activities and Protects Dopaminergic Neurons in Mouse Models of Parkinson’s Disease.” PLoS ONE 7, no. 6 (June 18, 2012). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377667/